F Rassoul

University of Leipzig, Leipzig, Saxony, Germany

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Publications (68)79.93 Total impact

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    ABSTRACT: The role of leukocyte adhesion molecules in patients with burns and their relationship to other parameters of inflammation and lipid metabolism is only recently beginning to be explored. Therefore, we investigated the temporal changes in the levels of soluble cell adhesion molecules and other parameters of inflammation and lipoprotein metabolism in patients with thermal injury. The serum levels of soluble adhesion molecules, intercellular cell adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin, C-reactive protein (CRP) and fibrinogen in seven patients with severe burns over a 30- day period were measured to determine the involvement of these factors in the pathophysiology of severe burns. Serum levels of slCAM-1, sVCAM-1 and sE-selectin were determined by ELISA. Furthermore, total cholesterol, high-density lipoprotein cholesterol (HDL chol), low-density lipoprotein cholesterol (LDL chol) and triglycerides (TG) were measured. Blood levels of sICAM-1, sVCAM-1, CRP and fibrinogen increased with maximum values six days after thermal injury. In contrast, serum levels of sE-selectin were elevated two days after thermal injury. The sICAM-1, sVCAM-1 and sE-selectin levels correlated significantly with both the CRP and the fibrinogen levels. Plasma total cholesterol, HDL cholesterol and LDL cholesterol decreased with minimum values four days after thermal injury. Furthermore, an increase of triglyceride levels was observed. The observed inflammatory response of soluble cell adhesion molecules could be useful in monitoring endothelial activation immediately following thermal injury. Further studies involving a larger number of patients with burns should help to clarify the extent to which measured parameters, especially the temporal changes ofsCAMs, could be relevant in assessing the morbidity ofpatients with thermal injury.
    The West Indian medical journal 11/2009; 58(5):417-21. · 0.32 Impact Factor
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    ABSTRACT: Numerous studies have identified hyperhomocysteinemia as an independent risk factor for coronary artery disease (CAD). Furthermore, influences of polymorphysim of methylenetetrahydrofolate reductase (MTHFR) on homocysteine levels are documented. However, the relationship between severity of CAD and polymorphism of MTHFR has not been systematically evaluated. The present study was undertaken to evaluate this relationship in patients undergoing coronary artery bypass surgery. Serum homocysteine and MTHFR polymorphism in relation to severity of CAD was examined in 113 male patients, who all underwent coronary artery bypass surgery. The prevalences of 677 C-->T transition of the MTHFR gene were determined in these patients. Two groups were compared according to GENSINI coronary score : mild atherosclerosis (CAD stenosis < 30) and severe atherosclerosis (CAD stenosis > 30). Patients with CAD showed a significantly higher serum concentration of homocysteine than control subjects (P < 0.01). The serum homocysteine level was significantly higher in patients with increased scores than in patients with mild CAD (Gensini score < 30) both with and without the MTHFR polymorphism. The findings of our study showed that hyperhomocysteinemia was significantly related to the severity of CAD independent on MTHFR polymorphism.
    The Indian Journal of Medical Research 03/2008; 127(2):154-8. · 2.06 Impact Factor
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    ABSTRACT: The consumption of omega-3 polyunsaturated fatty acids may protect against atherosclerotic diseases, and the blood concentrations of soluble cellular adhesion molecules (sCAMs) and endotbelin-1 (ET-1) possibly reflect the inflammatory processes underlying atherosclerosis. However, knowledge of the differential effects of dietary n-3 fatty acids on markers of inflammation is incomplete. Our aim was to compare the effects of dietary alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasma levels of endothelin-1 (ET-1). Therefore, a randomized strictly controlled dietary study in 48 healthy volunteers (mean age 25.9 years) with three dietary groups and a parallel design, consisting of two consecutive periods was conducted. Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids followed by
    CTNR. 11/2007; 5(4):189-195.
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    ABSTRACT: Population-based lipid screening studies were initiated in the city of Leipzig, Germany, and included more than 30,000 subjects. The objectives of the Lipid Study Leipzig (LSL) were to evaluate the cardiovascular risk factor profile and its dependence on age, nutrition and social factors. In addition, the study results were compared with those of other population-based studies, and the development of cardiovascular risk factors over a 10-year period was evaluated. LSL data were obtained from subjects recruited at community centres, work sites, schools and the University of Leipzig, Germany. Capillary blood cholesterol and high-density lipoprotein-cholesterol levels were measured using the Reflotron dry-chemistry system (Roche Diagnostics, Germany). Study data also included blood pressure, body mass index, waist-to-hip ratio, and the evaluation of dietary and lifestyle factors. The results of LSL show an age-dependent increase in cardiovascular risk, which may have been partly preventable. Furthermore, LSL showed an improvement in cardiovascular risk, with respect to plasma cholesterol, over the past 10 years in men and women older than 30 and 50 years, respectively. The known age dependence of total cholesterol and non-high-density lipoprotein-cholesterol is less pronounced for those following a healthy lifestyle and for vegetarians. This suggests that the age-dependent rise of these parameters is partly preventable.
    Experimental and clinical cardiology 01/2007; 12(1):51-3. · 1.10 Impact Factor
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    ABSTRACT: Inflammation plays an important role in both the initiation of atherosclerosis and development of atherothrombotic events. The adherence of leukocytes/monocytes to the endothelium is an early event in atherogenesis. Phytotherapeutica as garlic and garlic extracts were shown to have beneficial modulating effects in patients with atherosclerotic disease. The aim of this study was to evaluate in vitro the influence of water-soluble garlic (Allium sativum) extract on the cytokine-induced expression of endothelial leukocyte adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106). Cytokine-induced expression of cellular adhesion molecules was measured on primary human coronary artery endothelial cell (HCAEC) cultures. HCAEC were cultured in microvascular endothelial cell growth medium and preincubated with garlic extract at various concentrations (0.25-4.0 mg/ml), after which human interleukin-1alpha (IL-1alpha, 10 ng/ml) was added for 1 day. Fluorescein isothiocyanate (FITC)-labeled anti-ICAM-1 and FITC-labeled anti-VCAM-1 were used to analyze the IL-1alpha-induced expression of ICAM-1 and VCAM-1 by flow cytometry. Incubation of HCAEC with garlic extract significantly decreased ICAM-1 and VCAM-1 expression induced by IL-1alpha. In addition, we examined the effects of garlic extract on the adhesion of monocytes to endothelial cells, using the monocytic U937 cell line. The presence of garlic extract significantly inhibited the adhesion of monocytes to IL-1alpha-stimulated endothelial cells. These results indicate that garlic extract modulates the expression of ICAM-1 and VCAM-1, thus potentially contributing to the beneficial effects traditionally attributed to garlic.
    Phytomedicine 04/2006; 13(4):230-5. · 2.97 Impact Factor
  • Diabetologie Und Stoffwechsel - DIABETOL STOFFWECHS. 01/2006; 1.
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2006; 7(3):587-587.
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    ABSTRACT: Matrix‐assisted laser desorption and ionization time‐of‐flight (MALDI‐TOF) mass spectrometry (MS) was used to evaluate the lipid composition of human blood plasma. The focus was on parameters affecting the spectral quality: The laser intensity had the highest impact and must be set as low as possible. Additionally, salt removal by lipid extraction led to an enhanced reproducibility. Surprisingly, the influence of storage time of a given plasma sample was only weak. It will be shown that the lipid MALDI‐TOF mass spectra allow the differentiation of nutrition habits. The comparison between vegetarians and normal volunteers indicated a higher phosphatidylcholine to triacylglycerol and phosphatidylcholine to lysophosphatidylcholine ratio in the plasma of the vegetarians.
    Analytical Letters 12/2005; 39(6):1101-1113. · 0.97 Impact Factor
  • Fausi Rassoul, Heinz Löster, Volker Richter
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    ABSTRACT: L-Carnitine, L-(−)-β-hydroxy-γ-trimethylaminobutyrate, plays an important role as a factor necessary for the transport of long-chain fatty acids into the mitochondria. In order to investigate the influence of L-carnitine on hyperlipidaemias, the experimental model of the sucrose-induced hypertriglyceridaemia of the rat was used. In these experiments L-carnitine in the dose of 11 mg per day and 100 g body weight (over the period of 1 week) was able to antagonize the sucrose-induced hypertriglyceridaemia and the increase of serum free fatty acid level in female rats of the Wistar strain. Carnitine administration did not change the activities of lipogenic enzymes and fatty acid synthesis in the liver. However, L-carnitine increases the rate of hepatic fatty acid oxidation. Our results indicate a hypotriglyceridemic and free fatty acid lowering effect of L-carnitine, and suggest the use of this compound in the therapy of hyperlipidaemias.
    Monatshefte fuer Chemie/Chemical Monthly 01/2005; 136(8):1501-1507. · 1.63 Impact Factor
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    ABSTRACT: Age-dependent changes of lipid metabolism may arise both as a result of mechanisms of biological ageing and factors influencing age-dependent changes. To study possible influences of nutrition and life-style of vegetarians on age-dependence of lipid parameters, subjects of general population were compared with vegetarians. In the frame of population-based lipid screening projects in the city of Leipzig/Germany (Lipid Study Leipzig, LSL) 10 550 subjects (3,816 men and 6,734 women, age 18-99 years) of general population were compared with 417 vegetarians (vegans, lacto-vegetarians, lacto-ovo-vegetarians, 148 men and 269 women, age 18-93 years). Most of the vegetarians included in the study were members of the German Society of Vegetarians. The study program included capillary blood cholesterol measurements and the determination of high-density lipoprotein (HDL)-cholesterol, the measurement of other cardiovascular risk factors and the evaluation of dietary and life-style factors. Evaluation of cardiovascular risk profile within LSL was connected with individual consultation. The mean total cholesterol and non-HDL-cholesterol level and the total: HDL-cholesterol ratio showed the expected age-dependence, with maximum values within the decade 60-70 years. Vegetarians showed lower total and non-HDL-cholesterol levels in comparison with the general population. Furthermore, the age-dependent increase of these parameters is less pronounced under the conditions of vegetarian nutrition and life-style. Especially in young adulthood a significant difference is observed. Thus, the results of the present study reveal the role of nutritional and life-style factors that determine the lipid profile on a population basis and suggest that the known age-dependent rise of the level of atherogenic plasma lipoproteins is partly preventable.
    Zeitschrift für Gerontologie + Geriatrie 07/2004; 37(3):207-13. · 0.74 Impact Factor
  • Zeitschrift Fur Gerontologie Und Geriatrie - Z GERONTOL GERIATRIE. 01/2004; 37(3).
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    ABSTRACT: With respect to linoleic acid both beneficial and proatherogenic effects have been described. However, the effect on expression of cell adhesion molecules on human coronary artery endothelial cells (HCAEC) is not yet established. The aim of the experiments was to evaluate the influence of linoleic acid in comparison with palmitic acid regarding the cytokine-induced expression of endothelial leukocyte adhesion molecules (intercellular cell adhesion molecule-1 ICAM-1, vascular cell adhesion molecule-1 VCAM-1, E-selectin). HCAEC were cultured in microvascular endothelial cell growth medium. In the experiments, the cells were preincubated with linoleic acid and palmitic acid, respectively (10 micro mol/l, 2 days) or under control conditions, after which interleukin- 1alpha (IL-1alpha, 10 ng/ml in the test medium) was added for 1 day. The monoclonal antibodies used were fluorescein isothiocyanate (FITC)- labeled anti-ICAM-1, FITC-labeled anti-VCAM-1, and FITC-labeled anti-E-selectin. Expression was analyzed by flow cytofluorimetry. Next, to examine the effects of fatty acids on adhesion of monocytes to endothelial cells, adhesion experiments with the monocytic U 937 cell line were performed. IL-1alpha increased ICAM-1,VCAM-1, and E-selectin expression compared to controls. Incubation with IL-1alpha together with linoleic acid reduced the expression of ICAM-1 and VCAM-1 in contrast to palmitic acid. Furthermore, in the presence of linoleic acid a tendency of diminished adhesion of monocytes is seen. The results indicate that a reduced expression of cell adhesion molecules may be relevant to the antiatherogenic effects of linoleic acid. This is in contrast to the properties of palmitic acid.
    European Journal of Nutrition 09/2003; 42(4):224-7. · 3.13 Impact Factor
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    ABSTRACT: Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4-4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2-4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6-6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease ( n =19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.
    Clinical Science 02/2003; 104(2):189-93. · 4.86 Impact Factor
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    ABSTRACT: Elevated levels of circulating cell adhesion molecules (cCAMs) such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) are found in subjects with vascular diseases and in subjects with several risk factors for atherosclerosis. However, data evaluating cCAMs and biological age are limited. The purpose of this study was to assess in subjects with different cardiovascular risk profiles the levels of cVCAM-1, cICAM-1, and cE-selectin in dependence on age. The following groups of subjects were included in the study: 282 apparently healthy subjects of the average population aged 18-89 years, 77 vegetarians who are characterized by a favourable global cardiovascular risk profile, 94 patients with coronary heart disease, and 181 patients with peripheral arterial occlusive disease. Blood samples were obtained after an overnight fast for measurement of cCAMs, lipoproteins, and other clinical/biochemical parameters. The cCAM levels were determined by the use of monoclonal antibody based enzyme-linked immunosorbent assays. Amongst the cCAMs, cVCAM-1 is uniquely elevated in elderly persons with different risks for atherosclerosis, including subjects of the average population, vegetarians with a favourable risk profile, and patients with both coronary heart disease and peripheral arterial occlusive disease. With respect to cICAM-1, an age-dependent elevation was found in the control subjects included in the study. The cE-selectin levels were not correlated with age. Moreover, no associations of cCAMs with serum lipid and lipoprotein levels were found. The results of the present study indicate that cVCAM-1 is an age-dependent parameter independent of cardiovascular risk.
    Gerontology 01/2003; 49(5):293-300. · 2.68 Impact Factor
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    ABSTRACT: Increased plasma concentrations of circulating adhesion molecules in patients with Type II (non-insulin-dependent) diabetes mellitus could be associated with the increased cardiovascular risk in these patients. However, it is controversial whether increased adhesion molecule plasma concentrations are primarily related to hyperglycaemia or to hyperinsulinaemia. We evaluated the plasma concentrations of soluble E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) at baseline and during euglycaemic hyperinsulinaemic clamp in three different groups without additional cardiovascular risk factors: group A (control group), 28 healthy volunteers with normal glucose tolerance; group B, 24 subjects with fasting hyperinsulinaemia, normal fasting glucose but impaired glucose tolerance; group C, 32 patients with Type II diabetes, fasting hyperinsulinaemia and chronic hyperglycaemia. Plasma soluble E-selectin, ICAM-1, and VCAM-1 concentrations were higher ( p < 0.05) in patients with Type II diabetes (group C) compared with the other groups. The adhesion molecule concentrations correlate with the fasting plasma glucose ( r = 0.59, p < 0.001), the 2-h OGTT plasma glucose ( r = 0.70, p < 0.01), and the HbA(1 c) value ( r = 0.61, p < 0.05). The E-selectin but not the ICAM-1 and VCAM-1 plasma concentrations correlated with the fasting insulin concentrations ( r = 0.62, p < 0.05) or the whole body glucose uptake ( r = 0.59, p < 0.05) in the clamp. The hyperinsulinaemia during the euglycaemic hyperinsulinaemic clamp had no significant effect on the plasma concentrations of E-selectin, ICAM-1, and VCAM-1 in all three groups. Our results suggest that increased E-selectin concentrations are related to hyperglycaemia, hyperinsulinaemia and insulin resistance, whereas increased ICAM-1 and VCAM-1 plasma concentrations in patients with Type II diabetes are rather related to hyperglycaemia than to hyperinsulinaemia or insulin resistance.
    Diabetologia 02/2002; 45(2):210-6. · 6.49 Impact Factor
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    ABSTRACT: Upregulation of leukocyte adhesion molecules under atherogenic conditions is accompanied by the release of soluble forms of adhesion molecules into the bloodstream. Vegetarians have a favorable cardiovascular risk profile. The aim of the present study was to assess the levels of circulating E-selectin (cE-selectin), circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular adhesion molecule-1 (cVCAM-1) in both vegetarians and subjects of the average population and furthermore to evaluate the age dependence of cell adhesion molecules. 24 male and 59 female vegetarians (mainly members of the German Society of Vegetarians) and 124 male and 179 female control subjects (volunteers, of the ILSE study Leipzig = Interdisciplinary Long Time Study of Health Adult Age and the Lipid-Study Leipzig), 18-89 years old were included in the study. The serum levels of circulating cell adhesion molecules were determined using monoclonal antibody-based ELISA assays (R & D Systems, Abingdon, Europe Ltd.). Vegetarians were characterized by a favorable lipid profile and a low prevalence of common risk factors for atherosclerosis. This group showed a tendency towards lower cICAM-1 levels in comparison with control subjects. Furthermore, significantly lower cE-selectin levels were found in the group of vegetarians. An age-dependent increase of cVCAM-1 and cICAM-1 levels was found both in the group of vegetarians and control subjects. No significant differences were noted regarding the gender of the subjects included in the study. Low cE-selectin levels of vegetarians may reflect the favorable cardiovascular risk profile of this group. Furthermore, the present data indicate that cVCAM-1 and cICAM-1 are age-dependent parameters independent of risk for atherosclerosis.
    Zeitschrift für Gerontologie + Geriatrie 12/2001; 34(6):476-9. · 0.74 Impact Factor
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    ABSTRACT: Serum leptin levels reflect body fat mass (FM), and have been described to be related to serum uric acid levels in adult type 2 diabetic and healthy subjects. We therefore aimed to evaluate the interrelationship between leptin and markers of the metabolic syndrome by studying serum leptin concentration, body mass index (BMI), percent body fat (Fat%), total fat mass (FM), sum of skinfolds (SS), triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, insulin, calculated insulin resistance (HOMA), creatinine (CR), and uric acid (UA) concentration in 50 former small-for-gestational-age (SGA) children and 21 infants born adequate for gestational age (AGA) at the time of mid-puberty. Our data confirm previous results showing a positive association between leptin and body fatness, and female gender. Twelve children with impaired glucose tolerance (IGT) had higher UA levels than subjects with normal glucose tolerance (NGT) (5.1 +/- 1.1 v 4.2 +/- 1.2 mg/dL, P <.05), and showed the strongest relation between serum leptin and UA (r =.76, P <.001). Multiple regression analyses demonstrated that gender, estimates of total body adiposity (Fat% and SS), birth weight (BW), gestational age (GA), stimulated glucose and insulin, and serum UA are independently associated with serum leptin concentration in former SGA children with dysglycemia (R(2) =.89, P <.001). A long-term effect of intrauterine growth restriction on body fatness, metabolic syndrome, and serum leptin levels is suggested.
    Metabolism 10/2001; 50(10):1141-6. · 3.10 Impact Factor
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    ABSTRACT: Decreasing or eliminating animal products from the diet decreases the intake of some essential nutrients, such as vitamin B(12), which may lead to hyperhomocysteinemia. We investigated vitamin B(12)-dependent metabolism and oxidative stress in groups with various or no intake of meat or animal products. We investigated 44 high meat eaters, 19 low meat eaters, 34 lacto-ovo/lacto vegetarians, and 7 vegan vegetarians. Homocysteine (HCY) was assayed by HPLC, methylmalonic acid (MMA) by capillary gas chromatography-mass spectrometry, serum folate and vitamin B(12) with a chemiluminescence immunoassay, and total antioxidant status (TAS) by a Randox method. The mean serum HCY concentration of vegetarians was significantly increased, and in vegans the median concentration exceeded 15 micromol/L. Vegetarians had a higher serum concentration of MMA but a lower TAS. Vitamin B(12) and folate did not differ significantly between vegetarian and omnivorous subjects. Overall, HCY and MMA were significantly correlated. Vitamin B(12) correlated negatively with MMA, HCY, and folate, whereas the correlation with TAS was positive. Backward regression analysis revealed an independent influence of MMA on HCY, of HCY and vitamin B(12) on MMA, and of vitamin B(12) on TAS. The increased MMA concentration suggested a 25% frequency of functional vitamin B(12) deficiency in all vegetarians. Serum vitamin B(12) was below the lower reference limit in only five subjects. Functional vitamin B(12) deficiency in vegetarians may contribute to hyperhomocysteinemia and decreased TAS, which may partly counteract the beneficial lifestyle of vegetarians. However, increased serum HCY is most likely not responsible for the lower TAS values in vegetarians. We recommend assaying of MMA and HCY to investigate functional vitamin B(12) status.
    Clinical Chemistry 07/2001; 47(6):1094-101. · 7.15 Impact Factor
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    ABSTRACT: Seasonal variation in the plasma total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) have been repeatedly reported, with contradictory results regarding the pattern of seasonal variation of these parameters. Furthermore, it is still not well established whether the variation is due to changes in the nutrition or changes in physical activity depending on the season. The aim of this study was therefore to determine plasma TC and HDL-C in different groups of healthy participants: 19 vegetarians with a constant diet independent of the season, 14 athletes with almost constant physical activity over the year, and 114 controls in the age groups 20-26 years (mean age 24 + 1.5 years) and 40-48 years (mean age 44.3 + 2.1 years). Over 2 years, blood samples were collected every 2-3 months and were analyzed for plasma TC and HDL-C. At all visits, body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and nutrition and physical activity profiles were obtained. The seasonal model was calculated using object-oriented software for the analysis of longitudinal data in S (OSWALD); multiple regression analysis was used to determine the influence of age, gender, diet, and physical activity on seasonal changes of the lipid parameters. In all groups, we found an annual rhythm of the plasma TC and HDL-C concentrations, which can be mathematically described by a sine curve with a maximum in winter and a minimum in summer. This rhythm was independent of the age, gender, BMI, diet, or physical activity. The observed seasonal differences between the maximum and the minimum were about 5%-10% for TC and about 5%-8% for HDL-C concentration. These differences were greater than the determined circadian (TC 3.5%, HDL-C 4%) and day-to-day changes for TC and HDL-C (coefficient of variation <5% for both). In conclusion, annual rhythm of TC and HDL-C is not primarily induced by seasonal differences in dietary intake or physical activity. Therefore, the annual rhythm in cholesterol levels is most likely determined by endogenous factors or factors directly related to seasonal changes in the environment.
    Chronobiology International 06/2001; 18(3):541-57. · 4.35 Impact Factor
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    ABSTRACT: In order to suppress de novo cholesterol and VLDL biosynthesis, a long-term therapy trial with lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was initiated in two patients with cholesteryl ester storage disease (CESD), and concentrations of plasma lipids were monitored over a period of 9 years. We studied two male patients with enzymatically confirmed CESD in whom long-term lovastatin therapy (8 and 9 years) was begun at the age of 7 and 19 years. The diagnosis of CESD was confirmed by the measurement of human lysosomal acid lipase (hLAL) activity in cultured skin fibroblasts and leukocytes. Restriction fragment length polymorphism (RFLP) analysis revealed that both subjects are homozygotes for the common CESD splice site mutation. Levels of serum lipids and lipoproteins were measured yearly. During the first year, total serum cholesterol decreased from 317 to 201 mg/dl in Patient A and from 228 to 120 mg/dl in Patient B, due mainly to the reduction of low-density lipoprotein (LDL) cholesterol from 262 to 151 mg/dt in Patient A and from 166 to 66 mg/dl in Patient B. Accordingly, the LDL cholesterol : high density lipoprotein (HDL) cholesterol ratio was markedly reduced in both patients after one year of therapy. The treatment was continued and, after 9 years of further medication, low total cholesterol and LDL cholesterol levels were still maintained. The study demonstrates that HMG-CoA reductase inhibitors are well tolerated drugs during long-term treatment of CESD patients and may help to prevent the development of premature atherosclerosis.
    International journal of clinical pharmacology and therapeutics 06/2001; 39(5):199-204. · 1.20 Impact Factor

Publication Stats

350 Citations
79.93 Total Impact Points

Institutions

  • 1987–2009
    • University of Leipzig
      • • Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik
      • • Institut für Organische Chemie
      • • Medizinische Fakultät
      Leipzig, Saxony, Germany
  • 1982
    • Martin Luther University of Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany